SARS-CoV-2 non-structural protein 1 inhibits the interferon response by causing depletion of key host signaling factors

Type-I interferon (IFN) and IFN-stimulated genes are poorly induced in SARS-CoV-2 infected cells. Non-structural protein 1 (Nsp1) of SARS-CoV-2 blocks IFN induction by reducing phosphorylation and nuclear translocation of IRF3 that is essential for IFN-stimulated gene expression. Moreover, presumably by global host protein translational shut-off mechanism, the Nsp1 inhibits Tyk2 and STAT2 dependent induction of IFN-stimulated genes.